Plasminogen plays a key role in both physiological and pathological processes including inflammation and atherosclerosis. Cellular apoptosis plays a role in many of these processes as well. An emerging area of research suggests that plasminogen modulates apoptotic pathway(s). This proposal is based on preliminary data demonstrating that plasminogen retards apoptosis in monocytoid cells. However, the requirement for the proteolytic activity of plasmin in retardation of apoptosis has not been addressed. Additionally, the specific steps in the apoptotic pathway(s) that are modulated by plasminogen have not been elucidated. Knowledge of modulation of monocyte apoptosis by plasminogen is critical in understanding the physiological role of plasminogen, including clarifying the mechanisms of monocyte apoptosis. This knowledge may also be applied to the apoptotic processes implicated in inflammation and atherosclerosis. The central hypothesis to be addressed is that plasminogen retards monocyte apoptosis at discrete steps in the apoptotic pathway(s). This hypothesis is based on preliminary results, which demonstrate that the addition of plasminogen to monocytes significantly impedes apoptosis. [unreadable] [unreadable]